Social Profit Network, 250 Oak Grove Avenue, Menlo Park, CA 94025, USA.
Social Profit Network, 250 Oak Grove Avenue, Menlo Park, CA 94025, USA.
Arch Biochem Biophys. 2018 Dec 15;660:137-148. doi: 10.1016/j.abb.2018.10.013. Epub 2018 Oct 23.
It has been proposed that a loss of bioenergetic capacity of cells contributes to the progressive loss of biological function with age. Aging is associated with loss of mitochondrial cristae membranes and inhibition of ATP production. Despite the many approaches being pursued for improving mitochondrial function, none of them directly targets the electron transport chain to improve ATP production. Recent studies have brought attention to cardiolipin as a unique target for promoting mitochondrial efficiency. Cardiolipin is important for cristae curvatures and is necessary for optimal activity of the respiratory complexes and the assembly of supercomplexes. Here we describe the discovery of a class of cell-penetrating aromatic-cationic tetrapeptides that selectively target cardiolipin and increase coupling efficiency while reducing reactive oxygen species production. These compounds can rejuvenate mitochondrial bioenergetics, remodel mitochondrial cristae structure, repair cellular structure, and restore organ function during aging.
有人提出，细胞生物能量的丧失导致生物功能随着年龄的增长而逐渐丧失。衰老与线粒体嵴膜的丧失和 ATP 产生的抑制有关。尽管人们正在尝试许多方法来改善线粒体功能，但没有一种方法可以直接针对电子传递链来提高 ATP 产量。最近的研究引起了人们对心磷脂作为促进线粒体效率的独特靶点的关注。心磷脂对于嵴的弯曲度很重要，是呼吸复合物最佳活性和超复合物组装所必需的。在这里，我们描述了一类具有细胞穿透性的芳香阳离子四肽的发现，它们选择性地靶向心磷脂，提高偶联效率，同时减少活性氧的产生。这些化合物可以恢复线粒体生物能量，重塑线粒体嵴结构，修复细胞结构，并在衰老过程中恢复器官功能。
